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Neutrophil Delivered Hollow Titania Covered Persistent Luminescent Nanosensitizer for Ultrosound Augmented Chemo/Immuno Glioblastoma Therapy
Advanced Science ( IF 14.3 ) Pub Date : 2021-07-01 , DOI: 10.1002/advs.202004381 Yujie Li 1 , Xucong Teng 1 , Yongji Wang 1 , Chunrong Yang 1 , Xiuping Yan 2 , Jinghong Li 1
Advanced Science ( IF 14.3 ) Pub Date : 2021-07-01 , DOI: 10.1002/advs.202004381 Yujie Li 1 , Xucong Teng 1 , Yongji Wang 1 , Chunrong Yang 1 , Xiuping Yan 2 , Jinghong Li 1
Affiliation
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Glioblastoma (GBM) is the most malignant brain tumor with unmet therapeutic demand. The blood-brain-barrier (BBB) and tumor heterogeneity limit the treatment effectiveness of various interventions. Here, an ultrasound augmented chemo/immuno therapy for GBM using a neutrophil-delivered nanosensitizer, is developed. The sensitizer is composed of a ZnGa2O4:Cr3+ (ZGO) core for persistent luminescence imaging and a hollow sono-sensitive TiO2 shell to generate reactive oxygen species (ROS) for controlled drug release. Immune checkpoint inhibitor (Anti-PD-1 antibody) is trapped in the interior of the porous ZGO@TiO2 with paclitaxel (PTX) loaded liposome encapsulation to form ZGO@TiO2@ALP. Delivered by neutrophils (NEs), ZGO@TiO2@ALP-NEs can penetrate through BBB for GBM accumulation. After intravenous injection, ultrasound irradiation at GBM sites initiates ROS generation from ZGO@TiO2@ALP, leading to liposome destruction for PTX and anti-PD-1 antibody release to kill tumors and induce local inflammation, which in-turn attractes more ZGO@TiO2@ALP-NEs to migrate into tumor sites for augmented and sustained therapy. The treatment enhances the survival rate of the GBM bearing mice from 0% to 40% and endows them with long-term immuno-surveillance for tumor recurrence, providing a new approach for precision therapy against GBM and other cancers.
中文翻译：
中性粒细胞输送空心二氧化钛覆盖的持久发光纳米敏化剂，用于超声增强化疗/免疫胶质母细胞瘤治疗
胶质母细胞瘤（GBM）是最恶性的脑肿瘤，其治疗需求尚未得到满足。血脑屏障（BBB）和肿瘤异质性限制了各种干预措施的治疗效果。这里，开发了一种使用中性粒细胞递送的纳米敏化剂对 GBM 进行超声增强化疗/免疫疗法。该敏化剂由用于持久发光成像的ZnGa 2 O 4 :Cr 3+ (ZGO)核和用于产生活性氧(ROS)以控制药物释放的空心声敏TiO 2壳组成。免疫检查点抑制剂（抗PD-1抗体）被紫杉醇（PTX）负载的脂质体封装在多孔ZGO@TiO 2的内部，形成ZGO@TiO 2 @ALP。ZGO@TiO 2 @ALP-NEs由中性粒细胞 (NE) 传递，可以穿透 BBB 进行 GBM 积累。静脉注射后，GBM部位的超声照射启动ZGO@TiO 2 @ALP产生ROS ，导致PTX脂质体破坏和抗PD-1抗体释放，杀死肿瘤并诱导局部炎症，进而吸引更多的ZGO@ TiO 2 @ALP-NE 迁移到肿瘤部位以进行增强和持续治疗。该治疗将携带GBM的小鼠的存活率从0%提高到40%，并赋予它们对肿瘤复发的长期免疫监视，为针对GBM和其他癌症的精准治疗提供了新方法。
更新日期：2021-09-09
中文翻译：
中性粒细胞输送空心二氧化钛覆盖的持久发光纳米敏化剂，用于超声增强化疗/免疫胶质母细胞瘤治疗
胶质母细胞瘤（GBM）是最恶性的脑肿瘤，其治疗需求尚未得到满足。血脑屏障（BBB）和肿瘤异质性限制了各种干预措施的治疗效果。这里，开发了一种使用中性粒细胞递送的纳米敏化剂对 GBM 进行超声增强化疗/免疫疗法。该敏化剂由用于持久发光成像的ZnGa 2 O 4 :Cr 3+ (ZGO)核和用于产生活性氧(ROS)以控制药物释放的空心声敏TiO 2壳组成。免疫检查点抑制剂（抗PD-1抗体）被紫杉醇（PTX）负载的脂质体封装在多孔ZGO@TiO 2的内部，形成ZGO@TiO 2 @ALP。ZGO@TiO 2 @ALP-NEs由中性粒细胞 (NE) 传递，可以穿透 BBB 进行 GBM 积累。静脉注射后，GBM部位的超声照射启动ZGO@TiO 2 @ALP产生ROS ，导致PTX脂质体破坏和抗PD-1抗体释放，杀死肿瘤并诱导局部炎症，进而吸引更多的ZGO@ TiO 2 @ALP-NE 迁移到肿瘤部位以进行增强和持续治疗。该治疗将携带GBM的小鼠的存活率从0%提高到40%，并赋予它们对肿瘤复发的长期免疫监视，为针对GBM和其他癌症的精准治疗提供了新方法。
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